crossing96/oncoscreening huggingface dataset:
miRNAs associated with chemo-sensitivity in cell lines and in advanced bladder cancer.	BACKGROUND: MicroRNA is a naturally occurring class of non-coding RNA molecules that mediate posttranscriptional gene regulation and are strongly implicated in cellular processes such as cell proliferation, carcinogenesis, cell survival and apoptosis. Consequently there is increasing focus on miRNA expression as prognostic factors for outcome and chemotherapy response. Only approximately 50% of patients with bladder cancer respond to chemotherapy. Therefore, predictive markers, such as miRNAs, that can identify subgroups of patients who will benefit from chemotherapy will have great value for treatment guidance. METHODS: We profiled the expression of 671 miRNAs in formalin fixed paraffin embedded tumors from patients with advanced bladder cancer treated with cisplatin based chemotherapy. We delineated differentially expressed miRNAs in tumors from patients with complete response vs. patients with progressive disease and in tumors form patients with short and long overall survival time. Furthermore, we studied the effect of up- and down regulation of key miRNAs on the cisplatin sensitivity in eight bladder cancer cell lines with different sensitivities to cisplatin. RESULTS: miRNA expression profiling identified 15 miRNAs that correlated with response to chemotherapy and 5 miRNAs that correlated with survival time. Three miRNAs were associated with both response and survival (886-3p, 923, 944). By changing the cellular level of the response-identified miRNAs in eight bladder cell lines with different cisplatin sensitivity we found that down-regulation of miR-27a, miR296-5p and miR-642 generally reduced the cell viability, whereas up-regulation of miR-138 and miR-886-3p reduced the viability of more than half of the cell lines. Decreasing miR-138 increased the cisplatin sensitivity in half of the cell lines and increasing miR-27a and miR-642 generally increased cisplatin sensitivity. CONCLUSIONS: MiRNAs seem to be involved in cisplatin based chemo response and may form a new target for therapy and serve as biomarkers for treatment response.	bladder
Population-based study on prognostic factors for recurrence and progression in primary stage T1 bladder tumours.	OBJECTIVE: Stage T1 urothelial carcinoma of the bladder (UCB) exhibits heterogeneous clinical behaviour, and the treatment is controversial. The aim of this study was to evaluate prognostic factors for UCB in a defined, population-based cohort comprising patients with a first time diagnosis of primary stage T1 UCB. MATERIAL AND METHODS: The study population initially consisted of 285 patients with primary stage T1 UCB reported to the regional Bladder Cancer Registry in the Southeast Healthcare Region of Sweden from 1992 to 2001. The histological specimens were re-evaluated concerning stage, substaging of T1, World Health Organization (WHO) grade, lymphovascular invasion (LVI), tumour volume and total resected volume. Hospital records provided data on tumour size and multiplicity, occurrence of possible relapse and/or progression, death from UCB and whether treatment was given. RESULTS: After re-evaluation, the study population comprised 211 patients. The median follow-up time was 60 months. LVI was a prognostic factor for UCB progression and recurrence. Tumour size larger than 30 mm and multiplicity increased the risk of recurrence. T1 substaging, tumour volume and total resected volume were not associated with recurrence or tumour progression. CONCLUSIONS: LVI is significantly correlated with progression and recurrence in patients with primary stage T1 UCB. Therefore, the presence of LVI should be evaluated in every new case of T1 UCB.	bladder
Watchful waiting versus intravesical BCG therapy for high-grade pT1 bladder cancer with pT0 histology after second transurethral resection: Japan Clinical Oncology Group Study JCOG1019.	A Phase III clinical trial has been started in Japan to determine the optimal treatment strategy for patients with high-grade pT1 bladder cancer who have pT0 histology after second transurethral resection. The aim of this trial is to demonstrate the non-inferiority of relapse-free survival (excluding Tis or Ta intravesical recurrence) for watchful waiting compared with intravesical bacillus Calmette-Guérin therapy for pT0 after second transurethral resection. Patients with high-grade pT1 bladder cancer at the first registration and pT0 after second transurethral resection at the second registration are randomized to either a watchful waiting arm or an intravesical bacillus Calmette-Guérin therapy arm. A total of 575 patients at the first registration and 260 patients at the second registration will be accrued for this study from 38 institutions over 5 years. The primary endpoint is relapse-free survival (excluding Tis or Ta intravesical recurrence), and the secondary endpoints are overall survival, metastasis-free survival with bladder preserved, annual proportion of intravesical relapse-free survival, annual proportion of T2 or deeper relapse-free survival, adverse events and serious adverse events.	bladder
Plasma carotenoids and vitamin C concentrations and risk of urothelial cell carcinoma in the European Prospective Investigation into Cancer and Nutrition.	BACKGROUND: Published associations between dietary carotenoids and vitamin C and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. OBJECTIVE: We investigated the association between plasma carotenoids and vitamin C and risk of urothelial cell carcinoma (UCC) in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. DESIGN: A total of 856 patients with newly diagnosed UCC were matched with 856 cohort members by sex, age at baseline, study center, date and time of blood collection, and fasting status. Plasma carotenoids (α- and β-carotene, β-cryptoxanthin, lycopene, lutein, and zeaxanthin) were measured by using reverse-phase HPLC, and plasma vitamin C was measured by using a colorimetric assay. Incidence rate ratios (IRRs) were estimated by using conditional logistic regression with adjustment for smoking status, duration, and intensity. RESULTS: UCC risk decreased with higher concentrations of the sum of plasma carotenoids (IRR for the highest compared with the lowest quartile: 0.64; 95% CI: 0.44, 0.93; P-trend = 0.04). Plasma β-carotene was inversely associated with aggressive UCC (IRR: 0.51; 95% CI: 0.30, 0.88; P-trend = 0.02). Plasma lutein was inversely associated with risk of nonaggressive UCC (IRR: 0.56; 95% CI: 0.32, 0.98; P-trend = 0.05). No association was observed between plasma vitamin C and risk of UCC. CONCLUSIONS: Although residual confounding by smoking or other factors cannot be excluded, higher concentrations of plasma carotenoids may reduce risk of UCC, in particular aggressive UCC. Plasma lutein may reduce risk of nonaggressive UCC.	bladder
Small cell carcinoma of the urinary bladder.	Primary small cell carcinoma of the urinary bladder is very rare; only several studies have been reported in the English literature. A 62-year-old woman was admitted to our hospital because of hematuria and dysuria. Bladder endoscopy revealed a large polypoid tumor at the bladder base. Transurethral bladder tumorectomy (TUR-BT) was performed. Many TUR-BT specimens were obtained. Histologically, the bladder tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK8, CK18, neurone-specific enolase, chromogranin, NCAM (CD56), synaptophysin, Ki-67 (labeling=100%), p53, KIT (CD117), and platelet-derived growth factor receptor-α (PDGFRA). The tumor cells were negative for CK5/6, CK 34BE12, CK7, CK14, CK19, CK20, p63, CD45, and TTF-1. A molecular genetic analysis using PCR-direct sequencing showed no mutations of KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. No metastases were found by various imaging techniques. The patient is now treated by cisplatin-based chemotherapy.	bladder
Clinical features of bladder cancer in primary care.	BACKGROUND: Bladder cancer accounts for over 150,000 deaths worldwide. No screening is available, so diagnosis depends on investigations of symptoms. Of these, only visible haematuria has been studied in primary care. AIM: To identify and quantify the features of bladder cancer in primary care. DESIGN AND SETTING: Case-control study, using electronic medical records from UK primary care. METHOD: Participants were 4915 patients aged ≥40 years, diagnosed with bladder cancer January 2000 to December 2009, and 21,718 age, sex, and practice-matched controls, were selected from the General Practice Research Database, UK. All clinical features independently associated with bladder cancer using conditional logistic regression were identified, and their positive predictive values for bladder cancer, singly and in combination, were estimated. RESULTS: Cases consulted their GP more frequently than controls before diagnosis: median 15 consultations (interquartile range 9-22) versus 8 (4-15): P<0.001. Seven features were independently associated with bladder cancer: visible haematuria, odds ratio 34 (95% confidence interval [CI] = 29 to 41), dysuria 4.1 (95% CI = 3.4 to 5.0), urinary tract infection 2.2 (95% CI = 2.0 to 2.5), raised white blood cell count 2.1 (95% CI = 1.6 to 2.8), abdominal pain 2.0 (95% CI = 1.6 to 2.4), constipation 1.5 (95% CI = 1.2 to 1.9), raised inflammatory markers 1.5 (95% CI = 1.2 to 1.9), and raised creatinine 1.3 (95% CI = 1.2 to 1.4). The positive predictive value for visible haematuria in patients aged ≥60 years was PPV of 2.6% (95% CI = 2.2 to 3.2). CONCLUSION: Visible haematuria is the commonest and most powerful predictor of bladder cancer in primary care, and warrants investigation. Most other previously reported features of bladder cancer were associated with the disease, but with low predictive values. There is a need for improved diagnostic methods, for those patients whose bladder cancer presents without visible haematuria.	bladder
Diagnostic values of urine CYFRA21-1, NMP22, UBC, and FDP for the detection of bladder cancer.	BACKGROUND: We compared the diagnostic utilities of CYFRA 21-1, nuclear matrix protein-22 (NMP22), urinary bladder cancer antigen (UBC), and fibrin/fibrinogen degradation products (FDP) for detecting urinary bladder cancer. METHODS: We assayed CYFRA 21-1, NMP22, UBC and FDP from urine samples for 250 subjects. Among them, 54 were diagnosed as bladder cancer, and the remaining 196, which consisted of healthy individuals and patients with hematuria, inflammation/infection, or benign prostate hyperplasia, were assigned to the control group. RESULTS: Urinary levels of all 4 markers were higher in the bladder cancer group than the control group. The areas under the receiver operating characteristic curves (ROC-AUCs) of CYFRA 21-1, NMP22, UBC and FDP, corrected with urine creatinine concentrations, were 0.90, 0.89, 0.80 and 0.77, respectively, for discriminating bladder cancer from controls. The ROC-AUCs for the combinations of the markers were not significantly higher than those with CYFRA 21-1 or NMP22. NMP22 was the only independent variable for predicting bladder cancer among the four markers in the multivariate analysis. CONCLUSIONS: All 4 tumor biomarkers exhibited diagnostic utility for predicting bladder cancer. Among them, CYFRA 21-1 and NMP22 were the most effective at predicting bladder cancer.	bladder
Patterns of local recurrence after radical cystectomy in a contemporary series of patients with muscle-invasive bladder cancer.	PURPOSE: To describe the epidemiology, clinical features, and prognostic factors of local recurrence (LR) in a large case series of patients treated by radical cystectomy (RC) for bladder cancer. METHODS: A retrospective study was conducted on 903 patients treated in a single tertiary reference center. All cases of LR were identified. Descriptive analysis was performed on the clinical features, evolution, and overall mortality of these patients. Prognostic factors of LR were assessed using the Mann-Whitney test for continuous variables and the χ(2) test for categorical variables. RESULTS: Fifty-three patients were diagnosed with LR during follow-up (5.9 %). One patient had concomitant distant metastasis. Pain was the most frequent symptom leading to diagnosis. Mean time interval from RC to LR was 14.4 ± 13 months (1-64) with 50 % of cases diagnosed in the first postoperative year. Overall median survival of patients diagnosed with LR was 9 months [95 % confidence interval (6-11)]. Advanced pathological stage (T3 or T4) and lymph-node invasion were associated with increased LR rate in univariate and multivariate analysis. Presence of squamous cell carcinoma (SCC) was associated with a poorer prognosis after LR compared to pure urothelial carcinoma (p = 0.04). None of the parameters tested was associated with time interval between RC and LR diagnosis. CONCLUSIONS: LR is not uncommon, favored by high pathological stage (T3/T4), and has a very bad prognosis, particularly when SCC is present. LR must be carefully tracked during follow-up after RC, and optimal management of these cases remains to be determined.	bladder
Noninvasive micropapillary urothelial carcinoma: a clinicopathologic study of 18 cases.	Noninvasive micropapillary urothelial carcinoma consists of slender tufts of urothelial carcinoma lacking fibrovascular cores analogous to ovarian papillary serous tumors of borderline malignancy. Eighteen noninvasive micropapillary urothelial carcinoma cases were identified from the Pathology Department of The Johns Hopkins Hospital (2000-2011). Patients lacked history of invasive urothelial carcinoma. Two patterns of noninvasive micropapillary urothelial carcinoma were identified: (1) as a variant of noninvasive high-grade papillary urothelial carcinoma (high-grade papillary urothelial carcinoma/micropapillary urothelial carcinoma) (n = 13 cases) and (2) as a variant of urothelial carcinoma in situ (carcinoma in situ/micropapillary urothelial carcinoma) (n = 5 cases with 2 of these patients also having high-grade papillary urothelial carcinoma/micropapillary urothelial carcinoma). Of 18 patients, 16 (88%) were male with a mean age of 71.8 years (range, 54-87 years). Of the 12 patients initially treated with surveillance, Bacillus-Calmette Guérin, or intravesical chemotherapy, 4 did not recur and were without evidence of disease at 6, 21, 24, and 39 months. Four patients experienced recurrences with 3 of them without evidence of disease at 36, 52, and 72 months and with the fourth whose last follow-up was at 84 months when recurrence occurred. One patient is alive at 11 months with disease, and 1 died of other causes at 1 month. Two patients progressed to pT2 and pT3 disease at 5 and 21 months, respectively. It is critical to differentiate and clearly specify in pathology reports whether micropapillary urothelial carcinoma is invasive or noninvasive because invasive micropapillary urothelial carcinoma is an aggressive disease with a high degree of understaging, whereas some cases of noninvasive micropapillary urothelial carcinoma are not necessarily associated with an adverse outcome.	bladder
ICUD-EAU International Consultation on Bladder Cancer 2012: Urothelial carcinoma of the prostate.	CONTEXT: The Second International Consultation on Bladder Cancer recommendations on urothelial carcinoma (UC) of the prostate were presented at the 2011 European Association of Urology Congress in Vienna, Austria, on March 18, 2011. OBJECTIVE: Our aim is to summarize the Second International Consultation on Bladder Cancer recommendations on UC of the prostate to help clinicians assess the current evidence-based management. EVIDENCE ACQUISITION: The committee performed a thorough review of new data and updated previous recommendations. Levels of evidence and grades of recommendation were assigned based on a systematic review of the literature that included a search of online databases and review articles. EVIDENCE SYNTHESIS: Once a non-muscle-invasive high-grade tumor or carcinoma in situ (CIS) of the bladder has been diagnosed, careful follow-up of the prostatic urethra is necessary. Noninvasive UC including CIS of the prostate should be treated with intravesical bacillus Calmette-Guérin (BCG) following endoscopic resection. A transurethral resection of the prostate may improve contact of BCG with the prostatic urethra, and it appears that response rates to BCG are increased (level of evidence: 3). Transurethral biopsy of the prostatic urethra is effective in identifying prostatic involvement but may not accurately reveal the extent of involvement, particularly with stromal invasion. Stromal invasion by UC of the prostate carries a poor prognosis. Radical cystoprostatectomy is the treatment of choice for locoregional control in patients with prostatic stromal invasion. CONCLUSIONS: These recommendations contain updated information on the diagnosis and treatment of UC of the prostate. However, prospective trials are needed to further elucidate the best management of these patients.	bladder
Assessment and clinical significance of haematuria in Malaysian patients - relevance to early cancer diagnosis.	AIM: To study the causes and significance of both microscopic and macroscopic haematuria in adult patients and assess possible relevance to early detection of urological cancers. METHODS: 417 patients presenting with haematuria were assessed in our Urology Unit. Following confirmation of haematuria, these patients were subjected to imaging techniques and flexible cystoscopy. Parameters analysed included clinical characteristics, imaging results, flexible cystoscopy findings, time delay to diagnoses and eventual treatment and final diagnoses of all cases. RESULTS: 390 haematuria cases were analysed from 417 consecutive patients with haematuria. After 27 cases were excluded as they had previous history, 245 microscopic and 145 macroscopic. Age range was 17 to 95 years old with predominance of 152 females to 239 males. The racial distribution included 180 Chinese, 100 Indians,95 Malays and 15 other races. The final diagnoses were benign prostatic hyperplasia (22.6%), no cause found (22.3%), other causes (18.7%), urolithiasis (11.5%), urinary tract infection UTI (10.8%), non specific cystitis (10.3%), bladder tumours (2.8%) and other genitourinary tumours (1%). 11 new cases (2.8%) of bladder cancers were diagnosed, with a mean age of 59 years. Only 3 of 245 (1.2%) patients with microscopic haematuria had newly diagnosed bladder tumour compared with 8 of 145 (5.5%) patients with frank haematuria (p=0.016). Mean time taken from onset of symptoms to diagnosis of bladder cancer was 53.3 days with definitive treatment (TURBT) in 20.1 days from diagnosis. CONCLUSION: - This study has highlighted the common causes of haematuria in our local setting. We recommend that full and appropriate investigations be carried out on patients with frank haematuria especially those above 50 years old in order to provide earlier detection and prompt management of bladder diseases especially tumours.	bladder
Urothelial tumors of the urinary bladder in Manipur: a histopathological perspective.	OBJECTIVE: To study the histomorphological pattern of urothelial tumors of the urinary bladder in Manipur and to evaluate whether any correlation exists between tumor grade and muscle invasion. METHODS: A 10 year retrospective study of all consecutive cases diagnosed in the Department of Pathology RIMS - Imphal, between 1st January 2001 to 31st December 2010. RESULTS: The study included 26 cases of transitional cell tumors of urinary bladder. The male to female ratio was 1.5: 1 and the ages ranged from 38 years to 73 years (medians of 60 and 64 years, respectively). Of the total, 14 (53.9%) cases were low grade, 9 (34.6%) were high grade, 2 (7.7%) were papillomas and 1 (3.9%) was a papillary urothelial neoplasm of low malignant potential (PUNLMP). Pathological staging showed that 14 (53.9%) of the cases were stage PTa, four (15.4%) PT1, and eight (30.9%) PT2. Some 18.2% of low grade tumors and 75% of high grade tumors were invasive to the detrusor muscle layer. CONCLUSION: Bladder cancer is an uncommon disease, transitional tumors being the only histological type observed. It was more common in males than females, with peak incidence in seventh decade. Most of the tumors were non- invasive (PTa) and invasion to the detrusor muscle layer was seen in more than half of the high grade tumors. There is a definite correlation between advancing tumor grade and muscle invasion.	bladder
Influencing factors on the NMP-22 urine assay: an experimental model.	BACKGROUND: The commercial NMP-22 urine assays for bladder cancer (BCa) detect nuclear mitotic apparatus protein 1 (NUMA1) using monoclonal antibodies. It remains unclear whether these assays are monitoring a tumor antigen or some other phenomenon associated with the disease state. In this study, we investigated the influence of urinary cellular and protein concentration, and hematuria on the performance of the NMP-22 tests in an experimental model. METHODS: Pooled urine from healthy subjects were spiked with varying concentrations of benign (UROtsa) cells, cancer cells (RT4, T24, KU-7 and UM-UC-14), whole blood or serum, prior to analysis with both NMP22® Bladder Cancer ELISA test and the NMP22® BladderChek® point-of-care test. RESULTS: Urines from control subjects were negative for NMP-22. The addition of whole blood at 50ul/10 ml, but not serum, resulted in a false-positive result. Furthermore, the addition of a high concentration of benign urothelial cells (10(6)) or the cell lysate from these cells (306 μg protein) resulted in a false-positive result. High concentrations of pooled-cancer cells (10(6)) or cell lysate (30.6 μg and above) resulted in a positive NMP-22 assay. Concordance between the NMP-22 ELISA assay and the NMP-22 point of care assay was >90%. CONCLUSIONS: Rather than detecting a specific tumor antigen, urinary NMP-22 assays may be measuring the cellularity or amount of cell turnover that may be introduced into the urine by a variety of conditions, including surface shedding from bladder tumors. The absence of significant urinary cellularity in some cases due to lesion characteristics or the timing of sampling may result in false-negative NMP-2 assays.	bladder
Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.	Microsatellite markers are used for loss-of-heterozygosity, allelic imbalance and clonality analyses in cancers. Usually, tumor DNA is compared to corresponding normal DNA. However, normal DNA is not always available and can display aberrant allele ratios due to copy number variations in the genome. Moreover, stutter peaks may complicate the analysis. To use microsatellite markers for diagnosis of recurrent bladder cancer, we aimed to select markers without stutter peaks and a constant ratio between alleles, thereby avoiding the need for a control DNA sample. We investigated 49 microsatellite markers with tri- and tetranucleotide repeats in regions commonly lost in bladder cancer. Based on analysis of 50 blood DNAs the 12 best performing markers were selected with few stutter peaks and a constant ratio between peaks heights. Per marker upper and lower cut off values for allele ratios were determined. LOH of the markers was observed in 59/104 tumor DNAs. We then determined the sensitivity of the marker panel for detection of recurrent bladder cancer by assaying 102 urine samples of these patients. Sensitivity was 63% when patients were stratified for LOH in their primary tumors. We demonstrate that up-front selection of microsatellite markers obliterates the need for a corresponding blood sample. For diagnosis of bladder cancer recurrences in urine this significantly reduces costs. Moreover, this approach facilitates retrospective analysis of archival tumor samples for allelic imbalance.	bladder